Research on the synthesis and physiological evaluation of potential fluorinated volatile anesthetics will be shifted from halogenated 1,3-dioxolanes to linear diethers of the general formula CF3OROCF3 and halogenated dioxanes. We will study the reaction of carbonyl fluoride with ethylene glycol to form the bis-fluoroformate derivative, which will then be photochemically chlorinated to give compounds that can be separated and dehydrohalogenated with metallic zinc. The resulting olefinic structures will be treated with a variety of halogenating and hydrohalogenating agents and sulfur tetrafluoride to yield the corresponding bis-trifluoromethyl ethers as candidate anesthetics. By comparing the substituted 1,3-dioxolane series with the dioxane and linear dietheres as well as with the known alkyl and fluorinated alkyl ether anesthetics, we hope to establish a relationship between anesthetic index and the thermodynamic, conformational, and electronic environment of the fluorinated diethers. These considerations should give us a basis upon which to predict structures that will yield anesthetically potent compounds. All candidates will receive preliminary carcinogenicity screening and physiological evaluation.